Search

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is mainly caused by mutations in genes encoding desmosomal proteins. Variants in plakophilin-2 gene (PKP2) are the most common cause of the disease, associated with conventional ARVC phenotype. The study aims to evaluate the prevalence of PKP2 variants and examine genotype-phenotype correlation in Polish ARVC cohort. All 56 ARVC patients fulfilling the current criteria were screened for genetic variants in PKP2 using denaturing high-performance liquid chromatography or next-generation sequencing. The clinical evaluation involved medical history, electrocardiogram, echocardiography, and follow-up. Ten variants (5 frameshift, 2 nonsense, 2 splicing, and 1 missense) in PKP2 were found in 28 (50%) cases. All truncating variants are classified as pathogenic/likely pathogenic, while the missense variant is classified as variant of uncertain significance. Patients carrying a PKP2 mutation were younger at diagnosis (p = 0.003), more often had negative T waves in V1-V3 (p = 0.01), had higher left ventricular ejection fraction (p = 0.04), and were less likely to present symptoms of heart failure (p = 0.01) and left ventricular damage progression (p = 0.04). Combined endpoint of death or heart transplant was more frequent in subgroup without PKP2 mutation (p = 0.03). Pathogenic variants in PKP2 are responsible for 50% of ARVC cases in the Polish population and are associated with a better prognosis. ARVC patients with PKP2 mutation are less likely to present left ventricular involvement and heart failure symptoms. Combined endpoint of death or heart transplant was less frequent in this group., (© 2021. The Author(s).)

Congenital long QT syndrome (LQTS) is a primary cardiac channelopathy. Genetic testing has not only diagnostic but also prognostic and therapeutic implications. At present, 15 genes have been associated with the disease, with most mutations located in 3 major LQTS-susceptibility genes. During a routine genetic screening for KCNQ1, KCNH2 and SCN5A genes in index cases with LQTS, seven novel variants in KCNH2 and SCN5A genes were found. Genotype-phenotype correlations were analysed in these patients and their families. An open reading frame and splice site analysis of the exons was conducted using next-generation sequencing. In novel variants, phenotypes of carriers and their affected relatives were analysed. In 39 unrelated patients, 40 pathogenic/putative pathogenic mutations were found. Thirty-three of them, predominantly missense, were reported previously: 11 were in the KCNQ, 17 in the KCNH2 and 5 in the SCN5A gene. Seven novel missense variants were found in eight families. Among them, four variants were in typical for LQTS location. Two variants in the KCNH2 gene (p.D803Y and p.D46F) and one in the SCN5A gene (G1391R) were in amino acid (AA) position which up to present has not been reported in LQTS. Phenotype analysis showed the life-threatening course of the disease in index cases with a history of sudden cardiac death in six families. Mutation carriers presented with ECG abnormalities and some of them received beta-blocker therapy. We report three novel variants (KCNQ1 p.46, KCNH2 p.D803Y, SCN5A p.G1391R) which have never been reported for this AA location in LQTS; the phenotype-genotype correlation suggests their pathogenicity.

Introduction: Paragangliomas (PGLs) related to hereditary syndromes are rare mediastinal tumors. Paragangliomas are caused by mutations in genes encoding subunits of succinate dehydrogenase enzyme (SDH)., Aim: To evaluate clinical, anatomical and functional characteristics of mediastinal paragangliomas related to SDHx gene mutations., Material and Methods: Retrospective analysis of 75 patients with confirmed SDHx gene mutations (24 patients with SDHB , 5 SDHC , 46 with SDHD mutations) was performed. Patients underwent evaluation using computed tomography (CT), somatostatin receptor scintigraphy (SRS) ( 99m Tc-[HYNIC,Tyr3]-octreotide), 123 I mIBG scintigraphy and urinary excretion of total methoxycatecholamines., Results: Out of 75 patients, 16 (21%) patients (1 SDHB , 15 SDHD mutations) had 17 PGLs localized in the mediastinum. Fourteen PGLs were localized in the middle mediastinum (intrapericardial) and 3 PGLs in the posterior mediastinum. The median diameter of paragangliomas measured on the axial slice was 24.3 mm (interquartile range (IQR): 14.7-36.6), and the median volume was 2.78 ml (IQR: 0.87-16.16). Twelve out of 16 patients (75%) underwent SRS, and 11 of them (92.3%) had pathological uptake of the radiotracer. Eleven (68.75%) out of 16 patients underwent 123 I mIBG, with only 3 positive results. Symptoms of catecholamine excretion were observed in 3 patients with PGLs localized in the posterior mediastinum. All PGLs were benign except in 1 patient with the SDHB mutation and PGL detected in the posterior mediastinum, who had a metastatic disease., Conclusions: Most mediastinal paragangliomas were related to SDHD gene mutations. They were asymptomatic, localized in the medial mediastinum, intrapericardially.

Background: The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism is associated with the risk of primary hypertension (PH) and vascular complications in adults with PH., Methods: We explored the associations of the G894T polymorphism with 24-h ambulatory blood pressure, left ventricular mass (LVM), carotid intima media thickness (cIMT), urinary albumin excretion, oxidative stress and inflammatory parameters in 126 children with newly diagnosed PH and in 83 healthy children., Results: Among the 126 children with PH 92 (73%) had ambulatory hypertension and 34 (27%) had severe ambulatory hypertension. Left ventricular hypertrophy (LVH) was detected in 39 (31%) patients, cIMT of >2 standard deviation scores in 21 (16.6%) patients, albuminuria of >30 mg/24 h in 18 (14.3%) patients and metabolic syndrome (MS) in 22 (17.5%) patients. The frequency of the T allele was 52.4% in the PH group and 54.2% in the control group (not significant), and in both groups the frequency of the T allele was consistent with the Hardy-Weinberg equilibrium. Compared with G allele carriers, hypertensive T allele carriers had increased cIMT (p < 0.05) and more severe albuminuria (not significant, p = 0.1); there was no difference between the groups in hypertension severity and LVM. T and G allele distribution did not differ between patients with and without metabolic syndrome. No significant correlations between the assessed parameters and the eNOS G894T gene polymorphism were found in the controls, although T allele carriers tended to have an increased cIMT (p = 0.09)., Conclusion: The eNOS T allele is not more prevalent among hypertensive children than among healthy ones, but it is associated with early vascular damage in children with PH, independent of metabolic abnormalities. No associations between the eNOS G894T polymorphism and metabolic abnormalities were found.

Background and Aim: The aim of the report was to present a novel mutation in KCNH2 in a family with life-threatening long QT syndrome., Methods: A genetic study using the method of next generation sequencing was performed in a 47-year-old woman after several episodes of syncope and torsade de pointes after sudden stress, with familial history of sudden death in first-degree female relatives. The study was performed also in her three asymptomatic children. Prolongation of QTc and typical ECG pattern of long QT2 were seen in the index case and in her youngest son., Results: Novel mutations (p.F617V) in exon 7 of KCNH2 were found in the index case and in her youngest son., Conclusions: A novel heterozygous missense mutation in exon 7 of KCNH2 gene, causing a protein change p.F617V, was found in a family with life-threatening arrhythmias in women and clinical outcome typical for long QT2 syndrome.

Background: Recent advances in molecular biology have made it possible to identify numerous polymorphisms of the renin-angiotensin system, which play an important role in the etiology of cardiovascular disease., Objective: The aims of the study were (i) to assess the distribution of the angiotensin II type 1 receptor (AGTR1) gene 1166A/C polymorphism and two polymorphisms of the angiotensinogen (AGT) gene (Met235Thr and Thr174Met) in patients with ST-segment-elevation myocardial infarction (STEMI) who underwent coronary angiography, compared with healthy volunteers; (ii) to determine if there was any correlation between these polymorphisms and risk of STEMI; and (iii) to assess the association of the examined polymorphisms with such classic cardiovascular risk factors as hypertension, diabetes mellitus, obesity (based on a body mass index ≥25 kg/m2), smoking, dyslipidemia, and family history of cardiovascular disease., Methods: A total of 100 patients (mean age 57 ± 10 years [range 31-76 years]; 21% women) with diagnosed STEMI and a control group consisting of 95 healthy volunteers (mean age 38 ± 11 years [range 17-60 years]; 20% women) were investigated for the AGTR1 1166A/C polymorphism and two variants of AGT (Met235Thr and Thr174Met). All patients received standard therapy for STEMI., Results: There were significant differences in the distribution of genotypes and the AGT Met174 allele for AGT Thr174Met polymorphism between patients and healthy subjects (p < 0.05). The AGTR1 1166A/C polymorphism genotype frequencies were significantly different in patients with hypertension compared with normotensive individuals. Specifically, the AGTR1 1166 AA genotype was twice as common in patients with hypertension as in those without (67% vs 33%), while the AC and CC genotypes were found predominantly in normotensive patients (p = 0.0016). The variant 1166C allele was much more common in patients without hypertension (67%) than in patients with hypertension (33%; p = 0.0006). The variant AGT Thr235 allele was more common in patients without a family history of cardiovascular disease than in patients with this risk factor (p < 0.05). The odds ratio (OR) for STEMI in patients with the heterozygous AGT 174 Thr/Met genotype was increased to 1.884 (95% confidence interval [CI] 1.03, 3.446; p < 0.05), while the OR calculated for carriers of the AGT Met174 allele was 2.038 (95% CI 1.129, 3.68; p = 0.0182). Significant genotypic associations of combinations of renin-angiotensin system gene polymorphisms in STEMI were not observed., Conclusions: The most powerful predictive value for STEMI was represented by the Thr/Met genotype and the Met174 allele of the AGT Thr174Met gene polymorphism. In our study, in contrast to observations reported by other authors, the AA genotype of the AGTR1 1166A/C gene polymorphism - much more than other genotypes - was associated with hypertension.

Background: Common variants of the renin-angiotensin system (RAS) genes have been linked to a higher risk of coronary artery disease (CAD) and its complications., Aim: To determine the prognostic significance of a combination of three common polymorphisms of RAS genes (angiotensin converting enzyme - ACE Ins/Del, angiotensin receptor type 1 - AGT1R A1166C and angiotensinogen - ATG M235T) in patients with CAD., Methods: The study included 216 patients (mean age 58 ± 9 years, 74% male) prospectively followed for a mean 41 ± 17 months. The end-points were all-cause mortality, myocardial infarction, stroke or the need for coronary revascularisation., Results: An end-point occurred in 41 (19%) patients. None of the polymorphisms analysed separately was associated with the end-point. Odds ratios were calculated for different combinations of analysed alleles to determine their relation to outcomes. Based on the cut-off points of odds ratios, the study group was divided into three subgroups: 55 patients without ATG 235T allele (T- subgroup); 100 patients with ATG 235T allele alone or ATG 235T allele combined with ACE Del allele or AGT1R 1166C allele (T+ or T+1 subgroup); and 61 patients with all three variants (T+2 subgroup). Multivariate analysis showed that the only independent predictor of the endpoint was an increasing number of variant genes (HR = 2.6, 95% CI 1.4-4.9, p = 0.002)., Conclusions: Co-existing angiotensinogen M235T AGT polymorphism and two other common polymorphisms of the RAS genes are related to adverse events in patients with CAD.

Background: Coronary artery disease (CAD) is a complex disorder accounting for the majority of cardiovascular deaths and morbidity. It is believed that genetic factors explain part of the excessive risk of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI)., Aim: To evaluate the influence on long-term prognosis of some genetic polymorphisms affecting renin-angiotensin system, inflammatory response, beta-2 adrenergic receptor, nitric oxide and platelets activity in patients with stable CAD undergoing routine PCI., Methods: The study population consisted of 110 consecutive male patients with stable angina undergoing elective, single-vessel PCI. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism-based techniques. Follow-up data were obtained by postal questionnaires regarding survival, myocardial infarction and revascularisation procedures. The control group consisted of 78 healthy males., Results: Compared to controls, the distribution of polymorphisms among patients differed with regard to interleukin-1 receptor antagonist and CD14 variants. Patients who had PCI during follow-up in comparison with the remaining patients had a similar genetic profile, but higher triglycerides (1.9 vs 1.5 mmol/L, p = 0.01) and atherogenic index (3.8% vs 3.1%, p = 0.03) and lower percentage of HDL (21.8% vs 25.0%, p = 0.02). Among subjects with any revascularisation procedures, a similar clinical profile was observed. However, they differed from those without any procedures regarding the distribution of angiotensinogen M235T variants (MM%/TM%/TT%) 28%/64%/8% vs 19%/50%/31%, p = 0.048. Stratification for myocardial infarction showed association with selectin E variants (AA%/AC%/CC%) 57.1%/28.6%/14.3% vs 78.8%/21.2%/0%, p = 0.055 and higher triglycerides (2.11 vs 1.57 mmol/L, p = 0.055)., Conclusions: Although we cannot exclude the role of polymorphism in angiotensinogen and selectin E genes, the prognosis of patients post-PCI in our study was mainly influenced by risk factors related to lipid metabolisms.

Background: Dilated cardiomyopathy (DCM) is a disorder characterised by dilation and impaired contractility of the left or both ventricles. This multifactorial disease has a strong genetic component with familial occurrence. A number of genes have been associated with idiopathic DCM (IDCM) including beta-1 (b1-AR) and beta-2 (b2-AR) adrenergic receptors. b1-AR and b2-AR are G-coupled proteins which play an important role in the regulation of heart rate and cardiac contractility. The beta-adrenergic receptor pathway is altered in heart failure. Recent studies have discovered functionally relevant and common polymorphisms in both b1-AR and b2-AR., Aim: We investigated the frequency of the b1-AR (Ser49Gly, Arg389Gly) and b2-AR (Arg16Gly, Gln27Glu, Thr164Ile) polymorphisms in patients with IDCM in comparison to controls in the Polish population., Methods: We used a case-control study design comparing a series of consecutive, unrelated 97 IDCM patients with 105 healthy blood donors. Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP)., Results: There was no significant difference in relation to genotype distribution and allele frequencies of any analysed b1-AR and b2-AR polymorphisms between IDCM patients and controls. The analysis of polymorphism associations did not reveal a higher frequency of coexisting b2-AR Gly16Gln27, Gly16Glu27 and Arg16Gln27 genotypes alone or in combination with the b1-AR Arg389 allele in IDCM., Conclusion: Our data showed that the studied beta-adrenergic receptor polymorphisms did not seem to play a significant role in IDCM in the Polish population.

Background: Atheromatous renal artery stenosis (ARAS) often coexists with coronary artery disease (CAD). This study evaluated the prevalence of three polymorphisms: angiotensin-converting enzyme (ACE) insertion/deletion (Ins/Del), endothelial nitric oxide synthase (eNOS) Glu298Asp, and methylenetetrahydrofolate reductase (MTHFR) C677T, in hypertensive patients referred for coronary and renal angiography., Material/methods: The study included 223 hypertensive patients divided into three groups: 72 patients without significant CAD or evidence of ARAS, 111 patients with significant CAD but no ARAS, and 40 patients with coexisting significant CAD and evidence of ARAS. The control group consisted of 195 age- and sex-matched healthy subjects., Results: Patients with coexisting significant CAD and evidence of ARAS were older (p=0.03), less frequently obese (p=0.02), and more likely to have peripheral carotid or femoral artery disease (PAD) (p=0.02) compared with patients with significant CAD but no ARAS. They differed in terms of ACE Del/Del genotype distribution (40% vs. 17.1%, respectively, p=0.007). In a multivariate analysis the independent predictors of ARAS were PAD (OR: 3.7, 95%CI: 1.1-12.3, p=0.005) and ACE Del/Del polymorphism (OR: 3.3, 95%CI: 1.3-8.2, p=0.01). There was a higher prevalence of eNOS Asp/Asp genotype in all patients with significant CAD than in controls (9.3% vs. 3.6%, respectively, p=0.02), but no difference in MTHFR polymorphism between the studied groups was found., Conclusions: In the hypertensive population referred for coronary and renal angiography, the ACE insertion/deletion variant but not eNOS Glu298Asp or MTHFR C677T polymorphism, seems to coexist with atheromatous renal artery stenosis.

The prevalence of the familial defective apolipoprotein B-100 (FDB) Arg3500Gln mutation in 525 unrelated hypercholesterolaemic Polish subjects was evaluated. DNA samples were screened for FDB mutation using SSCP method. Presence of mutation was confirmed using a mismatch MspI PCR strategy. Plasma lipid levels and clinical characteristics of 13 patients identified as carriers of the mutation and of their 23 affected relatives were analysed and compared with non-affected ones. In the affected individuals a variable expression of lipid concentrations and of atherosclerosis symptoms were observed. The prevalence of FDB Arg3500Gln mutation in hypercholesterolaemic Polish subjects (3.7%) seems to be similar to the frequency reported in other Caucasian hypercholesterolaemic populations. The estimated prevalence of the mutation in general Polish population is relatively high being 1/250. The same haplotype at the apoB locus in the carriers of this mutation in Poland as in other populations from Western Europe suggests its common origin. In one hypercholesterolaemic subject a non-hitherto described mutation was identified. It consisted in C-->T transition in apoB codon 3492 leading to threonine to isoleucine substitution in 3492 position of apoB gene (Thr3492Ile).

The aim of this work was the determination of apolipoprotein(a) [Lp(a)] in the patients three months after the onset of ischaemic stroke. A group of 56 patients was investigated. Stroke was diagnosed as caused by atherosclerotic changes in main cerebral arteries in 32 patients and in 11 by changes in cervical arteries. In 13 persons a lacunar stroke was recognised. The mean Lp(a) level and the median value were significantly higher in the group of patients after stroke as compared with 45 controls. A more frequent occurrence of Lp(a) level over 30 mg/dl considered as pathological was observed more often in the patients. No correlation was seen between Lp(a) and the resistance of LDL to oxidation nor between Lp(a) and the amount of products of LDL oxidation in vitro.